Sodium Hydroxide → HCID 22561815, compound

HRID 1839599Notes

Reaction equation

HRID 1839599 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1B(O)O.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 6764944-BromoindoleHCID 27343342,4-Difluorophenylboronic acid

Product 1

HCID 22561815HCID 22561815, compoundYield 90.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-bromoindole (6.2 g, 31.7 mmol), and 2,4-difluorophenylboronic acid (5 g, 31.7 mmol) in THF (108 mL) were added Palladium catalyst Pd(PPh3)4 (0.67 g, 0.95 mmol) and the freshly prepared sodium hydroxide solution (3.8 g, 95 mmol in 45 mL of water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen at 80° C. oil bath for over the weekend. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed with brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified by a silica gel column to give 6.55 g (90%) of 4-(2,4-difluoro-phenyl)-1H-indole.

Workup

  1. customThe system was degassed
  2. additioncharged with nitrogen
  3. customthe completion of the coupling reaction
  4. temperatureThe mixture was cooled to room temperature
  5. customseparated from water layer
  6. washThe ethyl acetate solution was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration
  9. customthe solvents were evaporated
  10. customthe crude product was purified by a silica gel column

Sources & evidence

ORD record
ord-aef35fe1137d4eeb9cb64804c0716b70
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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